Establishment of etonitazene as a reinforcer for rats by use of schedule-induced drinking.

Drinking of etonitazene HCl by 6 rats was studied during daily 4-hr sessions. Five related experiments were conducted sequentially. In the first experiment schedule-induced polydipsia was established. Subsequently, etonitazene concentrations (1.25, 2.5 and 5.0 microgram/ml) were substituted for water, and intake of large quantities of the drug occurred. In the second experiment the concurrent food reinforcement schedule was discontinued and lever presses maintained by etonitazene (5 microgram/ml) persisted. In the third experiment the number of lever presses, required per dipper presentation of etonitazene (5 microgram/ml) was increased, and rate of lever pressing increased directly with the response requirement whereas number of dipper presentations remained constant. In the fourth experiment water was substituted for the 5 microgram/ml etonitazene solution. Water responding declined to low rates, but when etonitazene was reintroduced, responding increased to previous levels. Thus, etonitazene (5 microgram/ml) was functioning as a positive reinforcer. In the final experiment, progressive increases in the etonitazene concentration (5, 10, 20 and 40 microgram/ml) resulted in both systematic decreases in response rate and increases in quantity (microgram) consumed.